Proteinuria

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2]; Sapan Patel M.B.B.S; Ogheneochuko Ajari, MB.BS, MS [3]

Synonyms and keywords: Urinary protein levels raised; urine protein raised

Overview

Proteinuria (from protein and urine) means the presence of an excess of serum proteins in the urine. The protein in the urine often causes the urine to become foamy, although foamy urine may also be caused by bilirubin in the urine (bilirubinuria), retrograde ejaculation, pneumaturia (air bubbles in the urine) due to a fistula, or drugs such as pyridium.

Causes

Common Causes

• Glomerulonephritis
• IgA nephropathy
• Urinary tract infection

Causes by Organ System

Cardiovascular	Amyloidosis, Benign orthostatic (postural) proteinuria, Circulatory failure (see breathing difficulties), Constrictive pericarditis, Dehydration, Eclampsia, High blood pressure, Hypertension-related kidney failure, Nutcracker syndrome of left renal vein, Preeclampsia, Renal artery stenosis, Renal vein thrombosis, Shock, Subacute bacterial endocarditis, Tricuspid insufficiency
Chemical/Poisoning	Nitrosourea compounds, Toxic nephropathy
Dental
Dermatologic	No underlying causes
Drug Side Effect	Aflibercept, Anticonvulsants, Bevacizumab, Captopril, Carmustine, Caspofungin, Cisplatin, Deferasirox, Gemcitabine, Gold, Heavy metal ingestion, Heroin, Lomustine, Micafungin, Mithramycin, Nsaids, Pazopanib, Penicillamine, Sulphasalazine
Ear Nose Throat	No underlying causes
Endocrine	Diabetes mellitus, Hypothyroidism
Environmental	Allergens, Irradiation
Gastroenterologic	Cirrhosis of liver
Genetic	Alport syndrome, Alström syndrome, Aminoaciduria, Amyloidosis, Autosomal dominant conditions, Autosomal recessive conditions, Balkan endemic nephropathy, Congenital conditions, Connatal tulbulopathies, Cystinosis, Dent disease, Diabetes mellitus, Fabry's disease, Familial mediterranean fever, Galactosaemia, Genitourinary tuberculosis, Glycogen storage disease type i, Hepatorenal tyrosinaemia, Hereditary fructose intolerance, Idiopathic multicentric osteolysis, Imerslund-gräsbeck syndrome, Lecithin cholesterol acyltransferase deficiency, Nail patella syndrome, Polycystic kidney disease, adult (autosomal dominant), Recurrent hereditary polyserositis, Wilson's disease, X-linked hypophosphataemia
Hematologic	No underlying causes
Iatrogenic	No underlying causes
Infectious Disease	Epstein-barr virus, Helminthic, Hepatitis b, Hiv, Infectious mononucleosis, Legionella pneumophila, Leprosy, Malaria, Poststreptococcal glomerulonephritis, Prostitis, Pyelonephritis, acute, Subacute bacterial endocarditis, Toxoplasmosis, Urinary tract infection, Viruses and viral conditions, Yellow fever
Musculoskeletal/Orthopedic	No underlying causes
Neurologic	No underlying causes
Nutritional/Metabolic	No underlying causes
Obstetric/Gynecologic	No underlying causes
Oncologic	No underlying causes
Ophthalmologic	No underlying causes
Overdose/Toxicity	No underlying causes
Psychiatric	No underlying causes
Pulmonary	No underlying causes
Renal/Electrolyte	Amyloidosis, Bence-jones proteinuria, Crescentic gn, Dehydration, Fanconi syndrome, Fibrillary glomerulopathies, Focal segmental glomerulosclerosis (fsgs), Hyperoxaluria, Hypertension-related kidney failure, Hyperuricaemia, Hypokalemic nephropathy, Interstitial nephritis, Medullary cystic kidney disease, Myoglobinuria, Nephritic syndrome, Nephritis of pregnancy, Nephrotic syndromes (i.e. intrinsic renal failure), Papillary necrosis, Polycystic kidney disease, adult (autosomal dominant), Poststreptococcal glomerulonephritis, Proliferative glomerulonephritis, Proximal renal tubular acidosis, Pyelonephritis, acute, Renal artery stenosis, Renal metastases, Renal neoplasm, Renal tubular acidosis, Renal vein thrombosis, Rhabdomyolysis, Toxic nephropathy, Unilateral kidney, Urinary tract infection, X-linked hypophosphataemia
Rheumatology/Immunology/Allergy	Allergens, Arteriolar nephrosclerosis, Autoimmune conditions, Bence-jones proteinuria, Collagen vascular disease, Crescentic gn, Fanconi syndrome, Fibrillary glomerulopathies, Focal segmental glomerulosclerosis (fsgs), Henoch-schonlein syndrome, Hepatitis b, Iga nephropathy (i.e., berger's disease), Igm nephropathy, Increased formation of polyclonal free light chains, Interstitial nephritis, Mixed cryoglobulinemia, Multiple myeloma, [[Organ rejection- kidney transplant patients may have gamma-globulins in their urine if the kidneys start to reject.[8]]], Other vasculitis, Polyarteritis nodosa, Recurrent hereditary polyserositis, Rheumatoid disease, Sarcoidosis, Systemic lupus erythematosis, Systemic sclerosis, Wegener's granulomatosis
Sexual	No underlying causes
Trauma	No underlying causes
Urologic	Retrograde ejaculation
Miscellaneous	No underlying causes

Causes in Alphabetical Order

• Disease A
• Disease B
• Disease C
• Disease ...

• Disease P
• Disease Q
• Disease R
• Disease ...

• Disease X
• Disease Y
• Disease Z

Proteinuria may be a feature of the following conditions:

• Nephrotic syndromes (i.e. intrinsic renal failure)
• Pre-eclampsia
• Eclampsia
• Toxic lesions of kidneys
• Collagen vascular diseases(e.g., systemic lupus erythematosus)
• Dehydration
• Glomerular diseases, such as membranous glomerulonephritis, focal segmental glomerulonephritis, minimal change disease (lipoid nephrosis)
• Strenuous exercise
• Stress
• Benign Orthostatic (postural) proteinuria
• Focal segmental glomerulosclerosis (FSGS)
• IgA nephropathy (i.e., Berger's disease)
• IgM nephropathy
• Membranoproliferative glomerulonephritis
• Membranous nephropathy
• Minimal change disease
• Sarcoidosis
• Alport's syndrome
• Diabetes mellitus
• Drugs (e.g., NSAIDs, nicotine, penicillamine, gold, ACE inhibitors, antibiotics, opiates especially heroin.
• Fabry's disease
• Infections (e.g., HIV, syphilis, hepatitis,post-streptococcal infection)
• Aminoaciduria
• Fanconi syndrome
• Heavy metal ingestion
• Hypertensive nephrosclerosis
• Interstitial nephritis
• Sickle cell disease
• Hemoglobinuria
• Multiple myeloma
• Myoglobinuria
• Organ rejection- kidney transplant patients may have gamma-globulins in their urine if the kidneys start to reject.
• Ebola hemorrhagic fever
• Nail Patella syndrome
• Familial Mediterranean fever

Causes of Proteinuria by Classification

Glomerular Proteinuria

• Allergins
• Glomerulonephritis

• Minimal change GN
• Membranous GN
• Focal segmental GN
• Membranoproliferative GN
• Mesangioproliferative GN
• Fibrillary glomerulopathies
• Crescentic GN

• Collagen Vascular Disease

• Henoch-Schonlein Syndrome
• Kidney amyloidosis
• Mixed cryoglobulinemia
• Multiple Myeloma
• Other vasculitis
• Polyarteritis Nodosa
• Sarcoidosis
• Sickle Cell Disease
• Systemic lupus erythematosus
• Wegener's Granulomatosis

• Drugs
• Hereditary

• Anticonvulsants
• Captopril
• Gold
• Heavy metals
• Heroin
• NSAIDs
• Penicillamine

• Infections

• Bacterial
• CMV
• EBV
• Helminthic
• Hepatitis B
• HIV
• Leprosy
• Malaria
• Poststreptococcal glomerulonephritis
• Toxoplasmosis

• Miscellaneous

• Hypothyroidism
• Preeclampsia
• Nephritis of Pregnancy
• Nephritic syndrome
• Diabetes Mellitus

Tubular Proteinuria

• Connatal tulbulopathies
• Hypokalemic nephropathy
• Interstitial nephropathy
• Renal Vein Thrombosis
• Renal tubular acidosis
• Toxic nephropathy

Prerenal and Overflow Proteinuria

• Bence-Jones Proteinuria
  • Waldenstrom's macroglobulinemia
  • Chronic lymphocytic leukemia
  • Amyloidosis
  • Malignancies (e.g., lymphoma, other cancers)
  • Multiple myeloma
• Hemoglobinura
• Increased formation of polyclonal free light chains
• Myoglobinuria

Renal Parenchymal and Post Renal Proteinuria

• Hemmorhage in the urinary tract
• Local infections
• Nephrolithiasis
• Prostitis
• Tamm-Horsfall protein

Miscellaneous Causes of Proteinuria

• Arteriolar nephrosclerosis
• Chronic Pyelonephritis
• Constrictive Pericarditis
• Genitourinary Tuberculosis
• High Fever
• Malignant Hypertension
• Massive Obesity
• Orthostatic proteinuria
• Preeclampsia
• Renal Neoplasm
• Renal Vein Thrombosis
• Tricuspid insufficiency
• Unilateral kidney

Associated conditions

Proteinuria may be a sign of renal (kidney) damage. Since serum proteins are readily reabsorbed from urine, the presence of excess protein indicates either an insufficiency of absorption or impaired filtration. Diabetics may suffer from damaged nephrons and develop proteinuria.

With severe proteinuria, general hypoproteinemia can develop which results in diminished oncotic pressure. Symptoms of diminished oncotic pressure may include ascites, edema, and hydrothorax.

Diagnosis

Laboratory Findings

Proteinuria is often diagnosed by a simple dipstick test although it is possible for the test to give a false negative even with nephrotic range proteinuria if the urine is dilute. False negatives may also occur if the protein in the urine is composed mainly globulins or Bence-Jones Proteins because the reagent on the test strips, Bromphenol blue, is highly specific for albumin. Traditionally dipstick protein tests would be quantified by measuring the total quantity of protein in a 24-hour urine collection test, and abnormal globulins by specific requests for Protein electrophoresis.

Alternatively the concentration of protein in the urine may be compared to the creatinine level in a spot urine sample. This is termed Protein/Creatinine Ratio (PCR). The 2005 UK Chronic Kidney Disease guidelines states that PCR is a better test than 24 hour urinary protein measurement. Proteinuria is defined as a Protein:creatinine ratio >45 mg/mmol (which is equivalent to Albumin:creatinine ratio of >30 mg/mmol) with very high levels of nephrotic syndrome being for PCR > 100 mg/mmol.

Reference Range
Physiologic protien elimination	<150mg protien/24 hours
Proteinuria	>150mg protein/24 hours
Microalbuminuria	<30mg albumin/24 hours

Treatment

Treating proteinuria mainly needs proper diagnosis of the cause. The most common cause is diabetic nephropathy; in this case, proper glycemic control may slow the progression. Medical management consists of angiotensin converting enzyme (ACE) inhibitors, which are typically first-line therapy for proteinuria. In patients whose proteinuria is not controlled with ACE inhibitors, the addition of an aldosterone antagonist (i.e., spironolactone) or angiotensin receptor blocker (ARB) may further reduce protein loss. Caution must be used if these agents are added to ACE inhibitor therapy due to the risk of hyperkalemia. Proteinuria secondary to autoimmune disease should be treated with steroids or steroid-sparing agent plus the use of ACE inhibitors.

Related Chapters

• Albuminuria
• Microalbuminuria
• List of terms associated with diabetes